The Need for Rescue PCI after Failed Fibrinolysis: Who, When and Why.

Transcription

1 Implementing the pharmacoinvasive strategy in STEMI The Need for Rescue PCI after Failed Fibrinolysis: Who, When and Why. 7:20-7:40 Robert C. Welsh, MD, FRCPC, FESC, FAHA, FACC Professor of Medicine Director, Adult Cardiac Catheterization and Interventional Cardiology Co-Chair, Vital Heart Response Co-director, U of A Chest Pain Program

2 Disclosures: (previous 5 years) Research funding: Abbott Vascular, Astra Zeneca, Bayer, Boehringer Ingelheim, Bristol Myers-Squibb, Eli Lilly, Johnson and Johnson, Pfizer, Portola, Regado, Roche, sanofi aventis Consultant/honorarium: Abbott Vascular, Astra Zeneca, Bayer, Bristol Myers-Squibb, Edwards Lifesciences, Eli Lilly, Medtronic, Roche, sanofiaventis

3 Outline : Premises 1. Optimal STEMI care requires a dual reperfusion strategy (primary PCI and fibrinolysis) 2. Following fibrinolysis the pharmacoinvasive strategy improves outcomes and should be employed with: 1. Clinical vigilance for reperfusion success and urgent catheterization in the setting of reperfusion failure (rescue) or with early recurrent ischemia 2. Following successful pharmacological reperfusion a scheduled early angiography (6-24 hours) is warranted 3. An example of a real world pharmacoinvasive strategy - Vital Heart Response

4 Reperfusion Therapy Impact of Time to Treatment Classic Experiments in Animal Models -Ischemic necrosis begins within minutes of coronary occlusion -Reperfusion within the first hour salvages nearly two-thirds of the myocardium at risk thereafter abrupt declining such that little or no myocardial salvage is evident after three to six hours of occlusion. Reimer KA, Lowe JE, Rasmussen MM, et al. The wavefront phenomenon of ischemic cell death. 1. Myocardial infarct size vs duration of coronary occlusion in dogs. Circulation 1977; 56:

5 Primary Percutaneous Coronary Intervention Door-to-Balloon Time and Mortality in Patients Hospitalized with ST-Elevation Myocardial Infarction: Is 90 Minutes Fast Enough? Time (min) 30-d Mortality 1-Year Mortality 30 day mortality Adjusted Adjusted ( ) 8.8 ( ) ( ) 12.9 ( ) ( ) 16.6 ( ) N= ( ) 19.9 ( ) ( ) 22.9 ( ) 1 year mortality ( ) 25.5 ( ) ( ) 27.7 ( ) ( ) 29.5 ( ) ( ) 30.9 ( ) N=1932 Rathore SS, et al, Am J Cardiol Nov 1;104(9):

6 Time (min) Q3 10 STEMI Door-to-Balloon Times * Transfer In & Non-Transfer In Patients (not total ischemic times) >100,000 patients in >250 hospitals Q Transfer in DTB Times Caveat Total Ischemic Times Unreported Q Q2 11 Non-Transfer in DTB Times ACTION Registry-GWTG DATA: July 1, 2010 June 30, 2011

7 Baseline patient risk modulates optimal mode of reperfusion DANAMI 2: 3 Year Mortality 26% of patients high-risk (TIMI 5) FL 36.2% PPCI 25.3% P=0.02 FL=Fibrinolysis PPCI= Primary PCI TIMI <5 = 74% PPCI 8.0% FL 5.6% P=0.11 n = 1134 n = 393 Thune et al. Circulation 2005

8 A pooled analysis of an early fibrinolytic strategy versus primary PCI from CAPTIM and WEST One year survival by time to treatment p=0.021 FL<2h versus PCI<2h Westerhout et al, Am Heart J Feb;161(2):283-90

9 Premise 1 - Summary Primary PCI is the dominant reperfusion strategy but Timely primary PCI remains improbable for many STEMI patients despite improved time to treatment in regional STEMI programs Primary PCI is multi-disciplinary, time-sensitive, and its success if based on the operators experience 2. The majority of benefit of primary PCI over fibrinolysis is achieved in the approximately 25% of patients presenting with high risk features 3. The acceptable delay for withholding pharmacological reperfusion in anticipation of PCI is not static and is dependent upon individual patient and temporal characteristics In patients with clinical characteristics that predict complications of pharmacological reperfusion; a longer delay to Primary PCI is justified In early presenting patients (<3 hours) the acceptable delay is abbreviated

10 Pharmacoinvasive Strategy Definition Following evidence based fibrinolysis with appropriate conjunctive anticoagulant and antiplatelet therapy; Failure to Successfully Reperfuse Rescue angiography assessed as <50% ST resolution in the worst lead ST elevation at 90 minutes (60-90 minutes) Hemodynamic instability or refractory ventricular arrhythmia Urgent Angiography following successful reperfusion early (< 6 hours) recurrent ischemia Successful Reperfusion Scheduled angiography within 6-24 hours following successful fibrinolysis (>50% ST resolution in worst lead ST elevation) Armstrong et al, Am Heart J Jul;160(1):30-35

11 Pharmaco-invasive strategy Clinical endpoints at 6 12 months. Borgia F et al. Eur Heart J 2010;31:

12 Pharmaco-invasive strategy Safety endpoints. Borgia F et al. Eur Heart J 2010;31:

13 F. Van de Werf, ACC 2013

14 Dth/Shock/CHF/ReMI (%) PRIMARY ENDPOINT TNK vs PPCI Relative Risk 0.86, 95%CI ( ) PPCI 14.3% TNK 12.4% p=0.24 All cause death or shock or CHF or reinfarction up to day 30 Armstrong PW et al. NEJM, 2013

15 Premise 2 Summary 1. Following fibrinolysis the pharmacoinvasive approach improves outcomes compared to a conservative approach 2. A fibrinolytic pharmacoinvasive strategy is associated with similar outcomes to timely primary PCI

16 Reperfusion Failure Indication for Rescue PCI 6 mm 12 mm Baseline ECG Random ization TNK 90 min Post TNK ECG :40 08:51 08:51 10:28 22 Aug 2010 ECG Core Lab

17 Unpublished analysis Is the need for rescue PCI after fibrinolysis predictable? 1106 STEMI patients receiving FL from TRANSFER-AMI (n=885) and WEST (n=221) were combined to identify clinical variables and outcomes associated with Rescue PCI N=1106 Non-rescue PCI Rescue PCI P value N=772 N=334 Age year (IQR) 57.0 (50-66) 57.0 (50-67) 0.44 Independent predictors of Rescue PCI were: Males % Diabetes % Dyslipidemia % Prior MI OR 1.58 ( , p0.05), symptom to fibrinolysis OR 1.10 ( , p0.002) and anterior MI OR 1.18 ( , p0.23) however the discriminatory power was poor (c-index 0.56). Prior Angina % Prior MI % Anterior MI location % Time from symptom onset to FL (hrs) Time from FL to PCI (hrs) 6.6 (n=576/772) 3.7 (n=298/334) <0.001

18 Guideline adjudicated fibrinolytic failure: Incidence, findings and management in a contemporary clinical trial Buller CE et al., Am Heart J Jan;155(1):121-7.

19 Freedom from Death, remi, CHF, Stroke Success of Rescue PCI 427 STEMI Patients receiving lytic (60% SK, 26% RPA, 12% TPA, 2% TNK) & UFH and with <50% ST Res by 90 min 0.90 Rescue PCI 84.6% 95% Cl, P= Repeated thrombolysis 68.7% 95% Cl, Conservative therapy 70.1% 95% Cl, Rescue PCI conducted 4.6 hours following fibrinolysis Days After Randomization REACT. Gershlick A. et al. NEJM 2005;353:

20 Meta-analysis: Rescue PCI vs Conservative Tx Outcome Rescue PCI Conservative Treatment Mortality, % (n) HF, % (n) Reinfarction, % (n) Stroke, % (n) Minor bleeding, % (n) 7.3 (454) 12.7 (424) 6.1 (346) 3.4 (297) 16.6 (313) 10.4 (457) 17.8 (427) 10.7 (354) 0.7 (295) 3.6 (307) RR (95% CI) 0.69 ( ) 0.73 ( ) 0.58 ( ) 4.98 ( ) 4.58 ( ) P <.001 In 3 trials, enrolling 700 patients that reported the composite end point of all-cause mortality, reinfarction, and HF, rescue PCI was associated with a significant RR reduction of 28% (RR 0.72; 95% CI, ; P=.001) Wijeysundera HC, et al. J Am Coll Cardiol. 2007;49:

21 PCI Hospital Ambulance/ER STUDY PROTOCOL STEMI <3 hrs from onset symptoms, PPCI <60 min not possible, 2 mm ST-elevation in 2 leads RANDOMIZATION 1:1 by IVRS, OPEN LABEL Strategy A: pharmaco-invasive Strategy B: primary PCI <75y:full dose 75y: ½ dose TNK no lytic Aspirin Clopidogrel: LD 300 mg + 75 mg QD Enoxaparin: 30 mg IV + 1 mg/kg SC Q12h ECG at 90 min: ST resolution 50% YES angio >6 to 24 hrs PCI/CABG if indicated Aspirin Clopidogrel: 75 mg QD Enoxaparin: 0.75 mg/kg SC Q12h NO immediate angio + rescue PCI if indicated Antiplatelet and antithrombin treatment according to local standards Standard primary PCI Primary endpoint: composite of all cause death or shock or CHF or reinfarction up to day 30 F. Van de Werf, ACC 2013 Armstrong PW et al. NEJM, 2013

22 PCI Hospital Ambulance/ER STUDY PROTOCOL STEMI <3 hrs from onset symptoms, PPCI <60 min not possible, 2 mm ST-elevation in 2 leads RANDOMIZATION 1:1 by IVRS, OPEN LABEL Strategy A: pharmaco-invasive Strategy B: primary PCI <75y:full dose 75y: ½ dose TNK no lytic Aspirin Clopidogrel: LD 300 mg + 75 mg QD Enoxaparin: 30 mg IV + 1 mg/kg SC Q12h Aspirin Clopidogrel: 75 mg QD Enoxaparin: 0.75 mg/kg SC Q12h ECG at 90 min: ST resolution 50% YES NO CVC ECG core Lab immediate angio + angio Adjudication >6 to 24 hrs and site feedback rescue PCI if PCI/CABG if indicated indicated Antiplatelet and antithrombin treatment according to local standards Standard primary PCI Primary endpoint: composite of all cause death or shock or CHF or reinfarction up to day 30 F. Van de Werf, ACC 2013 Armstrong PW et al. NEJM, 2013

23 MEDIAN TIMES TO TREATMENT (min) min 29 9 Rx TNK 36% Rescue PCI at 2.2h 64% scheduled cath at 17h Sx onset 1st Medical contact Randomize IVRS Rx PPCI n= Hour 2 Hours 178 min Armstrong PW et al. NEJM, 2013

24 Impact of Rescue/Urgent Angiography on Outcomes of STEMI: Insights from STREAM Robert Welsh, Frans Van de Werf, Patrick Goldstein, Anthony Gershlick, Robert Wilcox, Thierry Danays, Erich Bluhmki, Cynthia Westerhout, Paul Armstrong American Heart Association Dallas, Texas Tuesday, November 19, 2013; 4:30 F. Van de Werf, ACC 2013

25 Reflections on STEMI care Research translation into practice ASSENT 3+ ( ) WEST ( ) Vital Heart Response ( onwards) - Established paramedic based pre-hospital fibrinolysis in Canada - Expanded pre-hospital reperfusion opportunities - Demonstrated the benefit of a systematic approach with abbreviated time to treatment and excellent clinical outcomes -A region wide systematic approach to STEMI care based on best evidence and regional expertise -Focused on earliest point of care

26 Vital Heart Response Contemporary Management of Acute MI Pre-hospital ambulance Pre-hospital fibrinolysis Pre-hospital triage for PCI or in-hospital fibrinolysis higher 0 Patient Risk Pre-hospital fibrinolysis Pre-hospital triage for in-hospital fibrinolysis lower Tertiary hospital Rescue PCI Transfer for Primary PCI Community hospital Adapted from Welsh et al AHJ, Jan 2003

27 Vital Heart Response Implementation of STEMI reperfusion resources to Central/Northern Alberta Total area 661,190 km2 Population 3.7 million Rapid diagnosis, triage and treatment

28 Vital Heart Response - Reperfusion Strategy Metropolitan (Metro) and Non-Metropolitan patients (Non-Metro) Shavadia et al. CJC, 2013

29 Vital Heart Response - In-hospital events Metropolitan (Metro) and Non-Metropolitan patients (Non-Metro) % Shavadia et al. CJC, 2013

30 Vital Heart Response Predictors of in-hospital events Multivariable logistic regression model 5 of the composite event of death, re-mi, cardiogenic shock and congestive heart failure Adjusted OR (95% CI) p-value Age (yrs) 1.03 (1.02, 1.04) < Hypercholesterolemia 0.74 (0.60, 0.90) Diabetes 1.75 (1.38, 2.21) < Non-metropolitan site 0.81 (0.50, 1.30) 0.37 Fibrinolysis 0.41 (0.26, 0.67) < The overall model is significant (LR χ 2 (6) = with p-value < ). The model fits the data well (Hosmer-Lemeshow χ 2 (6) = 1.17 with p-value = 0.979; C-statistic=0.66). Shavadia et al. CJC, 2013

31 Summary 1. In 2013, optimal STEMI care requires regional access to primary PCI and fibrinolysis with an individual patient risk - based reperfusion strategy 2. Following fibrinolysis the pharmacoinvasive strategy improves outcomes and should be employed within a dedicated STEMI system of care

32 Summary Pharmacoinvasive 3. Clinical vigilance for reperfusion success and urgent catheterization in the setting of reperfusion failure (rescue) or with early recurrent ischemia is warranted To date limited predictors exist for the need for rescue 4. Following successful fibrinolysis - scheduled early angiography (6-24 hours) should be encouraged Provides an optimal medical and interventional interplay with excellent patient outcomes and rational cost effective approach to revascularization